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"Worcester, MA - Current research suggests that TNF-receptor associated protein-1 (TRAP-1) may prevent cancer cell death. The related report by Leav et al, "Cytoprotective Mitochondrial Chaperone TRAP-1 as a Novel Molecular Target in Localized and Metastatic Prostate Cancer," appears in the January 2010 issue of the American Journal of Pathology. Prostate cancer cells are often resistant to cell death. Researchers led by Dr. Dario C. Altieri of the University of Massachusetts Medical School, therefore, explored the role of TRAP-1, a protein thought to regulate cell death, in prostate cancer survival. TRAP-1 was highly expressed in both high-grade human prostate cancer lesions and mouse models of prostate cancer, but not in benign or normal prostate tissue. In addition, TRAP-1 overexpression in non-cancer prostate cells inhibited cell death, whereas TRAP-1-deficient prostate cancer cells had enhanced levels of cell death. Moreover, treatment with Gamitrinib, which inhibits TRAP-1, resulted in prostate cancer cell death, but not death of non-cancerous prostate cells. Therefore, targeting TRAP-1 via Gamitrinib treatment may be a viable therapeutic strategy for patients with advanced prostate cancer."

Treatment of Metastatic Cancer with Tetrathiomolybdate, an Anticopper, Antiangiogenic Agent: Phase I Study -- Brewer et al. 6 (1): 1 -- Clinical Cancer Research

H. Weiler A platelet cloak for tumor cells Blood, January 1, 2005; 105(1): 5 - 6. Palumbo and colleagues show that platelets and fibrinogen protect metastatic tumor cells from elimination by NK cells, confirming a striking mechanistic link between activation of the blood coagulation system and the spread of tumor metastases

Review article: vitamin D acquisition and breast cancer risk. Pérez-López FR, Chedraui P, Haya J. Reprod Sci. 2009 Jan;16(1):7-19. Review. PMID: 19144887 DOI: 10.1177/1933719108327595 Conclusions: Although there are controversial results, it seems plausible that sufficient endogenous vitamin D levels may have a protective function on mammary cells, reducing breast cancer risk.

Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents. Pisanti S, Malfitano AM, Grimaldi C, Santoro A, Gazzerro P, Laezza C, Bifulco M. Best Pract Res Clin Endocrinol Metab. 2009 Feb;23(1):117-31. PMID: 19285265 doi:10.1016/j.beem.2009.02.001    

Singh RP, Agarwal R. Prostate cancer prevention by silibinin. Curr Cancer Drug Targets. 2004 Feb;4(1):1-11. Review. PMID: 14965263 [PubMed - indexed for MEDLINE]

The in vitro study, reported in the journal Carcinogenesis (Vol. 27, pp. 32-42), showed that vitamin D, in the form of the highly active 1alpha, 25-dihydroxyvitamin D3 (1,25-VD), inhibited the function of protease enzymes that are involved in tumour invasion. "We found that 1,25-VD decreased matric metalloproteinases (MMP-9) and cathepsins (CPs), while it [also] increased the activity of their counterparts, tissue inhibitors of metalloproteinase-1 (TIMP-1) and cathepsin inhibitors," wrote lead author Bo-Ying Bao from the University of Rochester and Taipei Medical University. "Mechanistic studies showed that 1,25-VD did not suppress MMP-9 expression at the transcriptional level, but reduced its mRNA stability," said Bao.

Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006 Jul;84(1):18-28. Review. PMID: 16825677

Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis.\nHolick MF.\nAm J Clin Nutr. 2004 Mar;79(3):362-71. Review. Erratum in: Am J Clin Nutr. 2004 May;79(5):890.\nPMID: 14985208

ScienceDaily (Sep. 1, 2005) - STANFORD, Calif. - The growth of prostate cancer cells can be halted by combining a form of vitamin D, available only by prescription, with low doses of an over-the-counter painkiller, researchers at the Stanford University School of Medicine have found. The combination reduced prostate cancer cell growth in a laboratory dish by up to 70 percent, according to the findings, published in the Sept. 1 issue of Cancer Research.

Brewer GJ, Merajver SD. Cancer therapy with tetrathiomolybdate: antiangiogenesis by lowering body copper--a review. Integr Cancer Ther. 2002 Dec;1(4):327-37. Review. PMID: 14664727 [PubMed - indexed for MEDLINE]

Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Michelakis ED, Webster L, Mackey JR. Br J Cancer. 2008 Oct 7;99(7):989-94. Epub 2008 Sep 2. Review. PMID: 18766181 doi:10.1038/sj.bjc.6604554 The unique metabolism of most solid tumours (aerobic glycolysis, i.e., Warburg effect) is not only the basis of diagnosing cancer with metabolic imaging but might also be associated with the resistance to apoptosis that characterises cancer. The glycolytic phenotype in cancer appears to be the common denominator of diverse molecular abnormalities in cancer and may be associated with a (potentially reversible) suppression of mitochondrial function. The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis. This reverses the suppressed mitochondrial apoptosis in cancer and results in suppression of tumour growth in vitro and in vivo. Here, we review the scientific and clinical rationale supporting the rapid translation of this promising metabolic modulator in early-phase cancer clinical trials More than 40 nonrandomised trials of DCA in small cohorts of patients have been reported, but the first two randomised control trials of chronic oral therapy with DCA in congenital mitochondrial diseases were reported in 2006. In the first, a blinded placebo-controlled study was performed with oral DCA administered at 25 mg kg-1 day-1 in 30 patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) (Kaufmann et al, 2006). Most patients enrolled in the DCA arm developed symptomatic peripheral neuropathy, compared with 4 out of 15 in the placebo arm, leading to the termination of the study. Seventeen out of 19 patients had at least partial resolution of peripheral neurological symptoms by 9 months after discontinuation of DCA. This neurotoxicity res

PHILADELPHIA - Researchers at Amgen are testing a fully human monoclonal antibody that inhibits the activity of insulin-like growth factors (IGF-1 and IGF-2) and appears to reduce pancreatic cancer cells in early testing, according to a report in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research.

Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, Jirousková M, Degen JL. Blood. 2005 Jan 1;105(1):178-85. Epub 2004 Sep 14. PMID: 15367435 DOI 10.1182/blood-2004-06-2272

In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus. Cho WC, Leung KN. J Ethnopharmacol. 2007 Aug 15;113(1):132-41. Epub 2007 May 31. PMID: 17611061 doi:10.1016/j.jep.2007.05.020    

Berberine and Coptidis rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations. Tang J, Feng Y, Tsao S, Wang N, Curtain R, Wang Y. J Ethnopharmacol. 2009 Oct 29;126(1):5-17. Epub 2009 Aug 15. PMID: 19686830 doi:10.1016/j.jep.2009.08.009 Conclusions The modern evidences of treating cancer with Huanglian and berberine have a strong linkage with traditional concept and rules of using Huanglian in CM practice. As anticancer candidates with low toxicity, berberine and its altered structure, as well as Huanglian and its formulae, will attract scientists to pursue the potential anticancer effects and the mechanisms by using technologies of genomics, proteomics and other advanced approaches. On the other hand, relatively few in vivo studies have been conducted on anticancer effects of Huanglian and berberine. The clinical application of berberine or Huanglian as novel cancer therapeutic agents requires in vivo validations and further investigations of their anticancer mechanisms.

Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Mantena SK, Sharma SD, Katiyar SK. Mol Cancer Ther. 2006 Feb;5(2):296-308. PMID: 16505103 doi: 10.1158/1535-7163.MCT-05-0448 The effectiveness of berberine in checking the growth of androgen-insensitive, as well as androgen-sensitive, prostate cancer cells without affecting the growth of normal prostate epithelial cells indicates that it may be a promising candidate for prostate cancer therapy. The evaluation of ancient herbal medicines may indicate novel strategies for the treatment of prostate cancer, which remains the leading cause of cancer-related deaths in American men (1). In our present investigation, we show that a naturally occurring isoquinoline alkaloid, berberine, significantly inhibits the proliferation and reduces the viability of DU145 and PC-3 as well as LNCaP cells (Fig. 1), which suggests that berberine may be an effective chemotherapeutic agent against both androgen-sensitive and androgen-insensitive prostate cancer cells. Importantly, we found that berberine did not exhibit toxicity to nonneoplastic human prostate epithelial cells under the conditions used, except for a moderate reduction in cell viability at higher concentrations when cells were treated in vitro for an extended period of time. In conclusion, the results of the present study indicate that berberine inhibits proliferation and induces G1-phase arrest and apoptosis in human prostate cancer cells but not in normal human prostate epithelial cells. In addition, we provide mechanistic evidence that berberine-induced apoptosis in prostate carcinoma cells, particularly hormone-refractory prostate carcinoma cells, is mediated through enhanced expression of Bax, disruption of the mitochondrial membrane potential, and activation of caspase-3.

Rosmarinic acid antagonizes activator protein-1-dependent activation of cyclooxygenase-2 expression in human cancer and nonmalignant cell lines. Scheckel KA, Degner SC, Romagnolo DF. J Nutr. 2008 Nov;138(11):2098-105. PMID: 18936204

Support ellagic acid therapy in patients with hormone refractory prostate cancer (HRPC) on standard chemotherapy using vinorelbine and estramustine phosphate. Falsaperla M, Morgia G, Tartarone A, Ardito R, Romano G. Eur Urol. 2005 Apr;47(4):449-54; discussion 454-5. Epub 2005 Jan 19. PMID: 15774240 doi:10.1016/j.eururo.2004.12.001

Aldehyde dehydrogenase 2 and head and neck cancer: a meta-analysis implementing a Mendelian randomization approach. Boccia S, Hashibe M, Gallì P, De Feo E, Asakage T, Hashimoto T, Hiraki A, Katoh T, Nomura T, Yokoyama A, van Duijn CM, Ricciardi G, Boffetta P. Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):248-54. PMID: 19124505 doi: 10.1158/1055-9965.EPI-08-0462